Dataset Information

Human brain LC-MS/MS - Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4+ T Cells in Multiple Sclerosis

ABSTRACT: Citrullination as a post-translational modification has been described in a couple of autoimmune diseases like rheumatoid arthritis (RA) and multiples sclerosis (MS). We investigated citrullination brain tissue from MS patients and healthy individuals (HD). The myelin sheath proteins have been the focus of citrullination and neurodegenerative diseases like Alzheimers Disease (AD), Parkinsons and MS. We analysed whole brain tissue of MS patients and HD and established a catalogue of citrullinated proteins. Besides new citrullinated proteins we found additional citrullinated sites on the already described proteins: MBP, GFAP and Vimentin.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, White Matter, Gray Matter

DISEASE(S): Multiple Sclerosis

SUBMITTER: Wolfgang Faigle

LAB HEAD: Prof. Dr. Roland Martin

PROVIDER: PXD008344 | Pride | 2019-04-10

REPOSITORIES: Pride

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Publications

Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4<sup>+</sup> T Cells in Multiple Sclerosis.

Faigle Wolfgang W Cruciani Carolina C Wolski Witold W Roschitzki Bernd B Puthenparampil Marco M Tomas-Ojer Paula P Sellés-Moreno Carla C Zeis Thomas T Jelcic Ivan I Schaeren-Wiemers Nicole N Sospedra Mireia M Martin Roland R

Frontiers in immunology 20190410

Immune responses to citrullinated peptides have been described in autoimmune diseases like rheumatoid arthritis (RA) and multiple sclerosis (MS). We investigated the post-translational modification (PTM), arginine to citrulline, in brain tissue of MS patients and controls (C) by proteomics and subsequently the cellular immune response of cerebrospinal fluid (CSF)-infiltrating T cells to citrullinated and unmodified peptides of myelin basic protein (MBP). Using specifically adapted tissue extract ...[more]

PMID: 31024521

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Project description:Citrullination is a post-translational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations and while the modification has been linked to several diseases including rheumatoid arthritis and cancer, its physiological or pathophysiological roles remain largely unclear. In part this is owing to limitations in available methodology able to robustly enrich, detect and localize the modification. As a result, only few citrullination sites have been identified on human proteins with high confidence. In this study, we mined data from mass spectrometry-based deep proteomic profiling of 30 human tissues to identify citrullination sites on endogenous proteins. Database searching of ~70 million tandem mass spectra yielded ~13,000 candidate spectra which were further triaged by spectrum quality metrics and the detection of the specific neutral loss of isocyanic acid from citrullinated peptides to reduce false positives. Because citrullination is easily confused with deamidation, we synthetised ~2,200 citrullinated and 1,300 deamindated peptides to build a library of reference spectra. This led to the validation of 375 citrullination sites on 209 human proteins. Further analysis showed that >80% of the identified modifications sites were new and for 56% of the proteins, citrullination was detected for the first time. Sequence motif analysis revealed a strong preference for Asp and Gly, residues around the citrullination site. Interestingly, while the modification was detected in 26 human tissues with the highest levels found in brain and lung, citrullination levels did not correlate well with protein expression of the PAD enzymes. Even though the current work represents the largest survey of protein citrullination to date, the modification was mostly detected on high abundance proteins arguing that the development of specific enrichment methods would be required in order to study the full extent of cellular protein citrullination.

Dataset Information

Human brain LC-MS/MS - Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4+ T Cells in Multiple Sclerosis

Publications

Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4<sup>+</sup> T Cells in Multiple Sclerosis.

Similar Datasets

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